lunes, 8 de abril de 2019

Unusual Cancers of Childhood Treatment (PDQ®) 3/5 —Health Professional Version - National Cancer Institute

Unusual Cancers of Childhood Treatment (PDQ®)—Health Professional Version - National Cancer Institute

National Cancer Institute



Unusual Cancers of Childhood Treatment (PDQ®)–Health Professional Version


Midline Tract Carcinoma Involving the NUT Gene (NUT Midline Carcinoma)

Molecular Features

NUT midline carcinoma is a very rare and aggressive malignancy genetically defined by rearrangements of the NUT gene. In most cases (75%), the NUT gene on chromosome 15q14 is fused with the BRD4 gene on chromosome 19p13, creating chimeric genes that encode the BRD-NUT fusion proteins. In the remaining cases, NUT is fused to BRD3 on chromosome 9q34 or to NSD3 on chromosome 8p11;[178] these tumors are termed NUT-variant.[179]

Clinical Presentation and Outcome

Childhood midline tract carcinomas (NUT midline carcinomas) arise in midline epithelial structures, typically mediastinum and upper aerodigestive tract, and present as very aggressive undifferentiated carcinomas, with or without squamous differentiation.[180,181] Although the original description of this neoplasm was made in children and young adults, individuals of all ages can be affected.[179] A retrospective series with clinicopathologic correlation found that the median age at diagnosis of 54 patients was 16 years (range, 0.1–78 years).[182]
The outcome is very poor, with a median survival of less than 1 year. Preliminary data suggest that NUT-variant tumors may have a more protracted course.[179,180]

Treatment of Childhood Midline Tract Carcinoma

Treatment options for childhood midline tract carcinoma include the following:
  1. Chemotherapy.
  2. Surgery.
  3. Radiation therapy.
Treatment of childhood midline tract carcinoma involving the NUT gene (NUT midline carcinoma) has included a multimodal approach with systemic chemotherapy, surgery, and radiation therapy. Cisplatin, taxanes, and alkylating agents have been used with some success; however, while early response is common, tumor progression occurs early in the course of the disease.[183]; [182][Level of evidence: 3iiiB] In a report from the NUT Midline Carcinoma Registry, 40 patients with primary tumors in the head and neck were evaluable. Two-year overall survival was 30%. The three long-term survivors (35, 72, and 78 months) underwent primary gross-total resection and received adjuvant therapy.[181][Level of evidence: 3iiA]
Preclinical studies have shown that the NUT-BRD4 fusion is associated with globally decreased histone acetylation and transcriptional repression; studies have also shown that this acetylation can be restored with histone deacetylase inhibitors, resulting in squamous differentiation and arrested growth in vitro and growth inhibition in xenograft models. Response to vorinostat has been reported in two separate cases of children with refractory disease, suggesting a potential role for this class of agents in the treatment of this malignancy.[184,185] The BET bromodomain inhibitors represent a promising class of agents that is being investigated for adults with this malignancy.[178]

Treatment Options Under Clinical Evaluation for Childhood Midline Tract Carcinoma

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following are examples of national and/or institutional clinical trials that are currently being conducted:
  • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 3,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.
    Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).
  • NCT01587703 (A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GSK525762 in Subjects With NUT Midline Carcinoma and Other Cancers): This study is evaluating the safety, pharmacokinetic, and pharmacodynamic profiles observed after oral administration of GSK525762, a BET bromodomain inhibitor, as well as the tolerability and clinical activity, in patients with NUT midline carcinoma and other solid tumors. Patients aged 16 years and older are eligible for this study.
  • NCT01987362 (A Two Part, Multicenter, Open-label Study of TEN-010 Given Subcutaneously): This is a phase I, nonrandomized, dose-escalating, open label, multicenter study of patients aged 18 years and older with histologically confirmed advanced solid tumors with progressive disease requiring therapy or NUT midline carcinoma. This study is evaluating the safety, tolerability, and pharmacokinetics of TEN-010, a small molecule bromodomain inhibitor.
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  112. Simard EP, Ward EM, Siegel R, et al.: Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin 62 (2): 118-28, 2012 Mar-Apr. [PUBMED Abstract]
  113. Gillison ML, Chaturvedi AK, Lowy DR: HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women. Cancer 113 (10 Suppl): 3036-46, 2008. [PUBMED Abstract]
  114. Guo T, Eisele DW, Fakhry C: The potential impact of prophylactic human papillomavirus vaccination on oropharyngeal cancer. Cancer 122 (15): 2313-23, 2016. [PUBMED Abstract]
  115. Morris LG, Ganly I: Outcomes of oral cavity squamous cell carcinoma in pediatric patients. Oral Oncol 46 (4): 292-6, 2010. [PUBMED Abstract]
  116. Perez DE, Pires FR, Alves Fde A, et al.: Juvenile intraoral mucoepidermoid carcinoma. J Oral Maxillofac Surg 66 (2): 308-11, 2008. [PUBMED Abstract]
  117. Oksüzoğlu B, Yalçin S: Squamous cell carcinoma of the tongue in a patient with Fanconi's anemia: a case report and review of the literature. Ann Hematol 81 (5): 294-8, 2002. [PUBMED Abstract]
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  121. Kraemer KH, Lee MM, Scotto J: Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol 123 (2): 241-50, 1987. [PUBMED Abstract]
  122. Alter BP: Cancer in Fanconi anemia, 1927-2001. Cancer 97 (2): 425-40, 2003. [PUBMED Abstract]
  123. Mazereeuw-Hautier J, Bitoun E, Chevrant-Breton J, et al.: Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients. Br J Dermatol 156 (5): 1015-9, 2007. [PUBMED Abstract]
  124. Alter BP, Giri N, Savage SA, et al.: Cancer in dyskeratosis congenita. Blood 113 (26): 6549-57, 2009. [PUBMED Abstract]
  125. Modh A, Gayar OH, Elshaikh MA, et al.: Pediatric head and neck squamous cell carcinoma: Patient demographics, treatment trends and outcomes. Int J Pediatr Otorhinolaryngol 106: 21-25, 2018. [PUBMED Abstract]
  126. Sturgis EM, Moore BA, Glisson BS, et al.: Neoadjuvant chemotherapy for squamous cell carcinoma of the oral tongue in young adults: a case series. Head Neck 27 (9): 748-56, 2005. [PUBMED Abstract]
  127. Woo VL, Kelsch RD, Su L, et al.: Gingival squamous cell carcinoma in adolescence. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107 (1): 92-9, 2009. [PUBMED Abstract]
  128. Sultan I, Rodriguez-Galindo C, Al-Sharabati S, et al.: Salivary gland carcinomas in children and adolescents: a population-based study, with comparison to adult cases. Head Neck 33 (10): 1476-81, 2011. [PUBMED Abstract]
  129. Cesmebasi A, Gabriel A, Niku D, et al.: Pediatric head and neck tumors: an intra-demographic analysis using the SEER* database. Med Sci Monit 20: 2536-42, 2014. [PUBMED Abstract]
  130. Chowdhry AK, McHugh C, Fung C, et al.: Second primary head and neck cancer after Hodgkin lymphoma: a population-based study of 44,879 survivors of Hodgkin lymphoma. Cancer 121 (9): 1436-45, 2015. [PUBMED Abstract]
  131. Boukheris H, Stovall M, Gilbert ES, et al.: Risk of salivary gland cancer after childhood cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys 85 (3): 776-83, 2013. [PUBMED Abstract]
  132. Rutt AL, Hawkshaw MJ, Lurie D, et al.: Salivary gland cancer in patients younger than 30 years. Ear Nose Throat J 90 (4): 174-84, 2011. [PUBMED Abstract]
  133. Allan BJ, Tashiro J, Diaz S, et al.: Malignant tumors of the parotid gland in children: incidence and outcomes. J Craniofac Surg 24 (5): 1660-4, 2013. [PUBMED Abstract]
  134. da Cruz Perez DE, Pires FR, Alves FA, et al.: Salivary gland tumors in children and adolescents: a clinicopathologic and immunohistochemical study of fifty-three cases. Int J Pediatr Otorhinolaryngol 68 (7): 895-902, 2004. [PUBMED Abstract]
  135. Muenscher A, Diegel T, Jaehne M, et al.: Benign and malignant salivary gland diseases in children A retrospective study of 549 cases from the Salivary Gland Registry, Hamburg. Auris Nasus Larynx 36 (3): 326-31, 2009. [PUBMED Abstract]
  136. Fu H, Wang J, Wang L, et al.: Pleomorphic adenoma of the salivary glands in children and adolescents. J Pediatr Surg 47 (4): 715-9, 2012. [PUBMED Abstract]
  137. Galer C, Santillan AA, Chelius D, et al.: Minor salivary gland malignancies in the pediatric population. Head Neck 34 (11): 1648-51, 2012. [PUBMED Abstract]
  138. Thariat J, Vedrine PO, Temam S, et al.: The role of radiation therapy in pediatric mucoepidermoid carcinomas of the salivary glands. J Pediatr 162 (4): 839-43, 2013. [PUBMED Abstract]
  139. Chiaravalli S, Guzzo M, Bisogno G, et al.: Salivary gland carcinomas in children and adolescents: the Italian TREP project experience. Pediatr Blood Cancer 61 (11): 1961-8, 2014. [PUBMED Abstract]
  140. Laikui L, Hongwei L, Hongbing J, et al.: Epithelial salivary gland tumors of children and adolescents in west China population: a clinicopathologic study of 79 cases. J Oral Pathol Med 37 (4): 201-5, 2008. [PUBMED Abstract]
  141. Rahbar R, Grimmer JF, Vargas SO, et al.: Mucoepidermoid carcinoma of the parotid gland in children: A 10-year experience. Arch Otolaryngol Head Neck Surg 132 (4): 375-80, 2006. [PUBMED Abstract]
  142. Kupferman ME, de la Garza GO, Santillan AA, et al.: Outcomes of pediatric patients with malignancies of the major salivary glands. Ann Surg Oncol 17 (12): 3301-7, 2010. [PUBMED Abstract]
  143. Aro K, Leivo I, Mäkitie A: Management of salivary gland malignancies in the pediatric population. Curr Opin Otolaryngol Head Neck Surg 22 (2): 116-20, 2014. [PUBMED Abstract]
  144. Ngouajio AL, Drejet SM, Phillips DR, et al.: A systematic review including an additional pediatric case report: Pediatric cases of mammary analogue secretory carcinoma. Int J Pediatr Otorhinolaryngol 100: 187-193, 2017. [PUBMED Abstract]
  145. Khalele BA: Systematic review of mammary analog secretory carcinoma of salivary glands at 7 years after description. Head Neck 39 (6): 1243-1248, 2017. [PUBMED Abstract]
  146. Locati LD, Collini P, Imbimbo M, et al.: Immunohistochemical and molecular profile of salivary gland cancer in children. Pediatr Blood Cancer 64 (9): , 2017. [PUBMED Abstract]
  147. Techavichit P, Hicks MJ, López-Terrada DH, et al.: Mucoepidermoid Carcinoma in Children: A Single Institutional Experience. Pediatr Blood Cancer 63 (1): 27-31, 2016. [PUBMED Abstract]
  148. Skálová A, Vanecek T, Sima R, et al.: Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol 34 (5): 599-608, 2010. [PUBMED Abstract]
  149. Verma J, Teh BS, Paulino AC: Characteristics and outcome of radiation and chemotherapy-related mucoepidermoid carcinoma of the salivary glands. Pediatr Blood Cancer 57 (7): 1137-41, 2011. [PUBMED Abstract]
  150. Védrine PO, Coffinet L, Temam S, et al.: Mucoepidermoid carcinoma of salivary glands in the pediatric age group: 18 clinical cases, including 11 second malignant neoplasms. Head Neck 28 (9): 827-33, 2006. [PUBMED Abstract]
  151. Ryan JT, El-Naggar AK, Huh W, et al.: Primacy of surgery in the management of mucoepidermoid carcinoma in children. Head Neck 33 (12): 1769-73, 2011. [PUBMED Abstract]
  152. Morse E, Fujiwara RJT, Husain Z, et al.: Pediatric Salivary Cancer: Epidemiology, Treatment Trends, and Association of Treatment Modality with Survival. Otolaryngol Head Neck Surg : 194599818771926, 2018. [PUBMED Abstract]
  153. Grant SR, Grosshans DR, Bilton SD, et al.: Proton versus conventional radiotherapy for pediatric salivary gland tumors: Acute toxicity and dosimetric characteristics. Radiother Oncol 116 (2): 309-15, 2015. [PUBMED Abstract]
  154. Mao MH, Zheng L, Wang XM, et al.: Surgery combined with postoperative (125) I seed brachytherapy for the treatment of mucoepidermoid carcinoma of the parotid gland in pediatric patients. Pediatr Blood Cancer 64 (1): 57-63, 2017. [PUBMED Abstract]
  155. Drilon A, Siena S, Ou SI, et al.: Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1). Cancer Discov 7 (4): 400-409, 2017. [PUBMED Abstract]
  156. Drilon A, Laetsch TW, Kummar S, et al.: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378 (8): 731-739, 2018. [PUBMED Abstract]
  157. Irace AL, Adil EA, Archer NM, et al.: Pediatric sialoblastoma: Evaluation and management. Int J Pediatr Otorhinolaryngol 87: 44-9, 2016. [PUBMED Abstract]
  158. Prigent M, Teissier N, Peuchmaur M, et al.: Sialoblastoma of salivary glands in children: chemotherapy should be discussed as an alternative to mutilating surgery. Int J Pediatr Otorhinolaryngol 74 (8): 942-5, 2010. [PUBMED Abstract]
  159. Scott JX, Krishnan S, Bourne AJ, et al.: Treatment of metastatic sialoblastoma with chemotherapy and surgery. Pediatr Blood Cancer 50 (1): 134-7, 2008. [PUBMED Abstract]
  160. Bitar MA, Moukarbel RV, Zalzal GH: Management of congenital subglottic hemangioma: trends and success over the past 17 years. Otolaryngol Head Neck Surg 132 (2): 226-31, 2005. [PUBMED Abstract]
  161. McGuirt WF Jr, Little JP: Laryngeal cancer in children and adolescents. Otolaryngol Clin North Am 30 (2): 207-14, 1997. [PUBMED Abstract]
  162. Bauman NM, Smith RJ: Recurrent respiratory papillomatosis. Pediatr Clin North Am 43 (6): 1385-401, 1996. [PUBMED Abstract]
  163. Pappo AS, Meza JL, Donaldson SS, et al.: Treatment of localized nonorbital, nonparameningeal head and neck rhabdomyosarcoma: lessons learned from intergroup rhabdomyosarcoma studies III and IV. J Clin Oncol 21 (4): 638-45, 2003. [PUBMED Abstract]
  164. Siddiqui F, Sarin R, Agarwal JP, et al.: Squamous carcinoma of the larynx and hypopharynx in children: a distinct clinical entity? Med Pediatr Oncol 40 (5): 322-4, 2003. [PUBMED Abstract]
  165. Kashima HK, Mounts P, Shah K: Recurrent respiratory papillomatosis. Obstet Gynecol Clin North Am 23 (3): 699-706, 1996. [PUBMED Abstract]
  166. Derkay CS, Wiatrak B: Recurrent respiratory papillomatosis: a review. Laryngoscope 118 (7): 1236-47, 2008. [PUBMED Abstract]
  167. Maloney EM, Unger ER, Tucker RA, et al.: Longitudinal measures of human papillomavirus 6 and 11 viral loads and antibody response in children with recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg 132 (7): 711-5, 2006. [PUBMED Abstract]
  168. Gélinas JF, Manoukian J, Côté A: Lung involvement in juvenile onset recurrent respiratory papillomatosis: a systematic review of the literature. Int J Pediatr Otorhinolaryngol 72 (4): 433-52, 2008. [PUBMED Abstract]
  169. Andrus JG, Shapshay SM: Contemporary management of laryngeal papilloma in adults and children. Otolaryngol Clin North Am 39 (1): 135-58, 2006. [PUBMED Abstract]
  170. Avidano MA, Singleton GT: Adjuvant drug strategies in the treatment of recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg 112 (2): 197-202, 1995. [PUBMED Abstract]
  171. Derkay CS, Smith RJ, McClay J, et al.: HspE7 treatment of pediatric recurrent respiratory papillomatosis: final results of an open-label trial. Ann Otol Rhinol Laryngol 114 (9): 730-7, 2005. [PUBMED Abstract]
  172. Sidell DR, Nassar M, Cotton RT, et al.: High-dose sublesional bevacizumab (avastin) for pediatric recurrent respiratory papillomatosis. Ann Otol Rhinol Laryngol 123 (3): 214-21, 2014. [PUBMED Abstract]
  173. Chadha NK, James A: Adjuvant antiviral therapy for recurrent respiratory papillomatosis. Cochrane Database Syst Rev 12: CD005053, 2012. [PUBMED Abstract]
  174. Ivancic R, Iqbal H, deSilva B, et al.: Current and future management of recurrent respiratory papillomatosis. Laryngoscope Investig Otolaryngol 3 (1): 22-34, 2018. [PUBMED Abstract]
  175. Young DL, Moore MM, Halstead LA: The use of the quadrivalent human papillomavirus vaccine (gardasil) as adjuvant therapy in the treatment of recurrent respiratory papilloma. J Voice 29 (2): 223-9, 2015. [PUBMED Abstract]
  176. Mészner Z, Jankovics I, Nagy A, et al.: Recurrent laryngeal papillomatosis with oesophageal involvement in a 2 year old boy: successful treatment with the quadrivalent human papillomatosis vaccine. Int J Pediatr Otorhinolaryngol 79 (2): 262-6, 2015. [PUBMED Abstract]
  177. Katsuta T, Miyaji Y, Offit PA, et al.: Treatment With Quadrivalent Human Papillomavirus Vaccine for Juvenile-Onset Recurrent Respiratory Papillomatosis: Case Report and Review of the Literature. J Pediatric Infect Dis Soc 6 (4): 380-385, 2017. [PUBMED Abstract]
  178. French CA, Rahman S, Walsh EM, et al.: NSD3-NUT fusion oncoprotein in NUT midline carcinoma: implications for a novel oncogenic mechanism. Cancer Discov 4 (8): 928-41, 2014. [PUBMED Abstract]
  179. French CA: NUT midline carcinoma. Cancer Genet Cytogenet 203 (1): 16-20, 2010. [PUBMED Abstract]
  180. French CA, Kutok JL, Faquin WC, et al.: Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol 22 (20): 4135-9, 2004. [PUBMED Abstract]
  181. Chau NG, Hurwitz S, Mitchell CM, et al.: Intensive treatment and survival outcomes in NUT midline carcinoma of the head and neck. Cancer 122 (23): 3632-3640, 2016. [PUBMED Abstract]
  182. Bauer DE, Mitchell CM, Strait KM, et al.: Clinicopathologic features and long-term outcomes of NUT midline carcinoma. Clin Cancer Res 18 (20): 5773-9, 2012. [PUBMED Abstract]
  183. Lemelle L, Pierron G, Fréneaux P, et al.: NUT carcinoma in children and adults: A multicenter retrospective study. Pediatr Blood Cancer 64 (12): , 2017. [PUBMED Abstract]
  184. Schwartz BE, Hofer MD, Lemieux ME, et al.: Differentiation of NUT midline carcinoma by epigenomic reprogramming. Cancer Res 71 (7): 2686-96, 2011. [PUBMED Abstract]
  185. Maher OM, Christensen AM, Yedururi S, et al.: Histone deacetylase inhibitor for NUT midline carcinoma. Pediatr Blood Cancer 62 (4): 715-7, 2015. [PUBMED Abstract]

Thoracic Cancers

Unusual pediatric thoracic cancers include the following:
The prognosis, diagnosis, classification, and treatment of these thoracic cancers are discussed below. It must be emphasized that these cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series.[1]

Breast Cancer

Fibroadenoma

Fibroadenoma is the most frequent breast tumor seen in children.[2,3] Sudden rapid enlargement of a suspected fibroadenoma is an indication for needle biopsy or excision, as rare transformation leading to malignant phyllodes tumors has been reported.[4]
Treatment of Fibroadenoma
Treatment options for fibroadenoma include the following:
  1. Observation. Many tumors will regress without a need for surgical resection.[3]
Treatment options for phyllodes tumors include the following:
  1. Wide local excision without mastectomy.[4]

Breast Cancer

Incidence and Outcome
Breast cancer has been reported in both males and females younger than 21 years.[5-11] A review of the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute shows that 75 cases of malignant breast tumors in females aged 19 years or younger were identified from 1973 to 2004.[12] Fifteen percent of these patients had in situ disease, 85% had invasive disease, 55% of the tumors were carcinomas, and 45% of the tumors were sarcomas—most of which were phyllodes tumors. Only three patients in the carcinoma group presented with metastatic disease, while 11 patients (27%) had regionally advanced disease. All patients with sarcomas presented with localized disease. Of the carcinoma patients, 85% underwent surgical resection, and 10% received adjuvant radiation therapy. Of the sarcoma patients, 97% had surgical resection, and 9% received radiation. The 5- and 10-year survival rates for patients with sarcomatous tumors were both 90%; for patients with carcinomas, the 5-year survival rate was 63% and the 10-year survival rate was 54%.
A National Cancer Database report described 181 cases of breast malignancy in patients aged 21 years and younger; 65% of patients had invasive carcinoma and the remaining patients had sarcoma or malignant phyllodes. In this study, the authors compared the pediatric patients with the adult patients and found that pediatric patients were more likely to have an undifferentiated malignancy, more advanced disease at presentation, and more variable management. Outcomes between children and adults were similar.[13]
While rare, breast cancer has also been described in males. In a review of the National Cancer Database, 677 male adolescents and young adults were diagnosed with breast cancer during the period of 1998 to 2010; most patients (82%) had invasive disease. Age younger than 25 years and absence of nodal evaluation at the time of surgery were associated with worse outcomes.[11]
Breast tumors may also occur as metastatic deposits from leukemia, rhabdomyosarcoma, other sarcomas, or lymphoma (particularly in patients who are infected with the HIV).
Risk Factors
Risk factors for breast cancer in adolescents and young adults (AYA) include the following:
  1. Previous malignancy. A retrospective review of the American College of Surgeons National Cancer Database from 1998 to 2010 identified 106,771 patients aged 15 to 39 years with breast cancer.[14] Of these patients, 6,241 (5.8%) had experienced a previous histologically distinct malignancy. Patients with breast cancer as a subsequent neoplasm had a significantly decreased 3-year overall survival (OS) (79% vs. 88.5%, P < .001), with subsequent neoplasm status identified as an independent risk factor for increased mortality (hazard ratio, 1.58; 95% confidence interval, 1.41–1.77).
  2. Chest irradiation. There is an increased lifetime risk of breast cancer in female survivors of Hodgkin lymphoma who were treated with radiation to the chest area; however, breast cancer is also seen in patients who were treated for any cancer that was treated with chest irradiation.[9,15-18][Level of evidence: 1A] Carcinomas are more frequent than sarcomas.
    Mammograms with adjunctive breast magnetic resonance imaging (MRI) start at age 25 years or 10 years postexposure to radiation therapy (whichever came last). (Refer to the PDQ summary on the Late Effects of Treatment for Childhood Cancer for more information about secondary breast cancers.)
Treatment of Breast Cancer in Adolescents and Young Adults
Breast cancer is the most frequently diagnosed cancer among AYA women aged 15 to 39 years, accounting for about 14% of all AYA cancer diagnoses.[19] Breast cancer in this age group has a more aggressive course and worse outcome than in older women. Expression of hormone receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER2) on breast cancer in the AYA group is also different from that in older women and correlates with a worse prognosis.[14,20]
Treatment of the AYA group is similar to that of older women. However, unique aspects of management must include attention to genetic implications (i.e., familial breast cancer syndromes) and fertility.[21,22]
(Refer to the PDQ summary on adult Breast Cancer Treatment or the PDQ summary on Genetics of Breast and Gynecologic Cancers for more information.)
Treatment Options Under Clinical Evaluation
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
  • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 3,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.
    Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).

Lung Cancer

Primary lung tumors are rare in children and histologically quite diverse.[1] When epithelial cancers of the lung occur, they tend to be of advanced stage, with prognosis dependent on both histology and stage.[23] Most primary lung tumors are malignant. In a review of 383 primary pulmonary neoplasms in children, 76% were malignant and 24% were benign.[24] A review of primary malignant epithelial lung tumors using the National Cancer Data Base found that the most common primary malignant pediatric lung neoplasms were carcinoid tumors (63%) followed by mucoepidermoid carcinoma of the lung (18%).[25]
Most pulmonary malignant neoplasms in children are due to metastatic disease, with an approximate ratio of primary malignant tumors to metastatic disease of 1:5.[26]
The following are the most common malignant primary tumors of the lung:

Tracheobronchial Tumors

Histology
Tracheobronchial tumors are a heterogeneous group of primary endobronchial lesions, and although adenoma implies a benign process, all varieties of tracheobronchial tumors on occasion display malignant behavior. The following histologic types have been identified (refer to Figure 4):[27-33]
  • Carcinoid tumor (neuroendocrine tumor of the bronchus). Carcinoid tumors account for 80% to 85% of all tracheobronchial tumors in children.[27-31] It is the most common tracheobronchial tumor.
  • Mucoepidermoid carcinoma. A slow-growing vascular polypoid mass of the airway that is the second most common (10%) pediatric tracheobronchial tumor.
  • Inflammatory myofibroblastic tumors. These low-grade benign tumors account for 1% of pediatric tracheobronchial tumors, are commonly located in the upper trachea, and rarely metastasize.
  • Rhabdomyosarcoma.
  • Granular cell tumors. Malignant transformation has not been documented in pediatric patients.
ENLARGEDrawing showing the most representative primary tracheobronchial tumors in children: myofibroblastic inflammatory tumor, carcinoid, rhabdomyoma, granular cell tumor, and mucoepidermoid K.
Figure 4. The most representative primary tracheobronchial tumors are described with their more frequent location. Reprinted from Seminars in Pediatric Surgery, Volume 25, Issue 3, Patricio Varela, Luca Pio, Michele Torre, Primary tracheobronchial tumors in children, Pages 150–155, Copyright (2016), with permission from Elsevier.
Prognosis
With the exception of rhabdomyosarcoma, tracheobronchial tumors of all histologic types are associated with an excellent prognosis after surgical resection in children, even in the presence of local invasion.[34,35]; [36][Level of evidence: 2A]
Clinical Presentation and Diagnostic Evaluation
The presenting symptoms of a tracheobronchial tumor are usually caused by an incomplete tracheobronchial obstruction and include the following:
  • Cough.
  • Recurrent pneumonitis.
  • Hemoptysis.
Because of difficulties in diagnosis, symptoms are frequently present for months, and, occasionally, children with wheezing have been treated for asthma, with delays in diagnosis for as long as 4 to 5 years.[37]
Metastatic lesions are reported in approximately 6% of carcinoid tumors, and recurrences are reported in 2% of cases. Atypical carcinoid tumors are rare but more aggressive, with 50% of patients presenting with metastatic disease at diagnosis.[23,38] There is a single report of a child with a carcinoid tumor and metastatic disease who developed the classic carcinoid syndrome.[39] Octreotide nuclear scans may demonstrate uptake of radioactivity by the tumor or lymph nodes, suggesting metastatic spread.
The management of tracheobronchial tumors is somewhat controversial because tracheobronchial tumors are usually visible endoscopically. Biopsy of these lesions may be hazardous because of the risk of hemorrhage. New endoscopic techniques have allowed biopsy to be performed safely;[32,40] however, endoscopic resection is not recommended except in highly selected cases.[33,40,41] Bronchography or computed tomography scan may be helpful to determine the degree of bronchiectasis distal to the obstruction since the degree of pulmonary destruction may influence surgical therapy.[42]
Treatment
Conservative pulmonary resection, including sleeve segmental resection, when feasible, with the removal of the involved lymphatics, is the treatment of choice.[43,44]; [36][Level of evidence: 2A] Chemotherapy and radiation therapy are not indicated for tracheobronchial tumors, unless evidence of metastasis is documented or the tumor is the rhabdomyosarcoma histologic type.
Treatment options for tracheobronchial tumors, according to histologic type, are as follows:
  1. Carcinoid tumor (neuroendocrine tumor of the bronchus). Surgical resection with lymph node sampling is the treatment of choice. OS is 95%.[45,46]
  2. Mucoepidermoid carcinoma. The recommended treatment is open surgical resection and lymph node sampling. Endoscopic resection is not recommended.[33,47]
  3. Inflammatory myofibroblastic tumors. Surgery is the treatment of choice. However, if the tumor is ALK mutation-positive, treatment with crizotinib may be effective.[33,48-50]
  4. Rhabdomyosarcoma. Mutilating surgery is not indicated. This tumor is very responsive to chemotherapy and radiation therapy, even with lymph node metastasis.[33]
  5. Granular cell tumors. Surgical resection is based on morbidity risk.[33,51,52]
(Refer to the Neuroendocrine Tumors [Carcinoid Tumors] section of this summary for information about neuroendocrine carcinoid tumors.)
Treatment Options Under Clinical Evaluation
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
  • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 3,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.
    Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).

Pleuropulmonary Blastoma

Types of Pleuropulmonary Blastoma
Pleuropulmonary blastoma is a rare and highly aggressive pulmonary malignancy that can present as a pulmonary or pleural mass. In most cases, pleuropulmonary blastoma is associated with germline mutations of the DICER1 gene. The International Pleuropulmonary Blastoma Registry is a valuable resource for information on this rare malignancy.[53,54]
The following three subtypes of pleuropulmonary blastoma have been identified:
  • Type I: A purely lung cystic neoplasm with subtle malignant changes that typically occurs in the first 2 years of life and has a good prognosis. The median age at diagnosis for Type I tumors is 8 months, and it has a slight male predominance. Transition from Type I to Type III occurs; however, a significant proportion of Type I lesions may not progress to Type II and Type III tumors.[54,55]
    Histologically, these tumors appear as a multilocular cyst with variable numbers of primitive mesenchymal cells beneath a benign epithelial surface, with skeletal differentiation in one-half of the cases.[55] This form of disease can be clinically and pathologically deceptive because of its resemblance to some developmental lung cysts.
  • Type Ir: A purely cystic tumor that lacks a primitive cell component. The r designation signifies regression or nonprogression. Type Ir was originally recognized in older siblings of pleuropulmonary blastoma patients, but can be seen in very young children. A lung cyst in an older individual with a DICER1 mutation or in a relative of a pleuropulmonary blastoma patient is most likely to be Type Ir.[54]
    In the Pleuropulmonary Blastoma Registry experience, most Type I and Ir cysts are unilateral (74%), half are unifocal, and 55% are larger than 5 cm. Pneumothorax may be present at diagnosis in up to 30% of Type I and Ir pleuropulmonary blastoma cases.[54]
  • Type II: Type II exhibits both cystic and solid components. The solid areas have mixed blastomatous and sarcomatous features; most of the cases exhibit rhabdomyoblasts, and nodules with cartilaginous differentiation are common.[56]
    Anaplasia is present in up to 60% of the cases.[57] In the Pleuropulmonary Blastoma Registry, the median age at diagnosis was 35 months, and distant metastases were present at the time of diagnosis in 7% of cases.[54]
  • Type III: A purely solid neoplasm, with the blastomatous and sarcomatous elements described above, and the presence of anaplasia in 70% of cases.[57-59]
    Median age at diagnosis in the Pleuropulmonary Blastoma Registry was 41 months, and distant metastases were present in 10% of patients at the time of diagnosis.[54]
The Pleuropulmonary Blastoma Registry reported on 350 centrally reviewed and confirmed cases of pleuropulmonary blastoma over a 50-year period (refer to Table 3).[54]
Table 3. Relative Proportions and Features of Pleuropulmonary Blastomaa
 Type IType IrType IIType II/III or III
aAdapted from Messinger et al.[54]
Relative proportion of pleuropulmonary blastoma cases33%35%32%
Presence of germline DICER1mutation62%63%75%
Median age at diagnosis (months)8473541
5-year overall survival89%100%71%53%
Prognostic Factors
In a comprehensive analysis of 350 patients reported by the Pleuropulmonary Blastoma Registry, only two prognostic factors were identified: the type of pleuropulmonary blastoma and the presence of metastatic disease at diagnosis.[54] (Refer to Table 3.) In three additional small cohort series, the ability to perform a complete surgical resection was also identified as a prognostic factor.[60-62]
The presence of a germline DICER1 mutation is not a prognostic factor.[54]
Risk Factors
Close to two-thirds of patients with pleuropulmonary blastoma have a germline DICER1mutation. Approximately one-third of families of children with pleuropulmonary blastoma manifest a number of dysplastic and/or neoplastic conditions comprising the DICER1 syndrome.[63-65] Most mutation carriers are unaffected, indicating that tumor risk is modest.[64]
Germline DICER1 mutations have been associated with the following:[63-67]
  • Cystic nephroma and Wilms tumor. Up to 10% of pleuropulmonary blastoma cases have been reported to develop cystic nephroma or Wilms tumor, which are the most relevant associated malignancies. These tumors are also more prevalent among family members.[68]
  • Ovarian sex cord–stromal tumors (especially Sertoli-Leydig cell tumor).
  • Multinodular goiter.
  • Uterine cervix embryonal rhabdomyosarcoma.
  • Nasal chondromesenchymal hamartoma.
  • Renal sarcoma.
  • Pulmonary sequestration.
  • Juvenile intestinal polyps.
  • Ciliary body medulloepithelioma.
  • Medulloblastoma.
  • Pineoblastoma.
  • Pituitary blastoma.
  • Seminoma.
DICER1 mutations appear to have a low penetrance, with pleuropulmonary blastoma, cystic nephroma, and multinodular goiter being the most frequently reported manifestations. Most associated conditions occur in children younger than 10 years, although ovarian tumors and multinodular goiters are described in children and adults aged up to 30 years.[65,67] Surveillance and screening recommendations have been proposed.[67]
Clinical Presentation
Presenting symptoms are not specific, and commonly include the following:
  • Respiratory distress.
  • Fever.
  • Chest pain.
The tumor is usually located in the lung periphery, but it may be extrapulmonary with involvement of the heart/great vessels, mediastinum, diaphragm, and/or pleura.[60,61] Tumor embolism is a known risk, and radiographic evaluation of the central circulation is performed to identify potentially fatal embolic complications.[69]
Treatment
There are no standard treatment options. Current treatment regimens for these rare tumors have been informed by consensus opinion.
Treatment options for pleuropulmonary blastoma include the following:
  1. Surgery.
  2. Adjuvant chemotherapy.
A complete surgical resection is required for cure.[60]
Data from the International Pleuropulmonary Blastoma Registry and from the European Cooperative Study Group in Pediatric Rare Tumors (EXPeRT) suggest that adjuvant chemotherapy may reduce the risk of recurrence.[54]; [61][Level of evidence: 3iiiA] Responses to chemotherapy have been reported with agents similar to those used for the treatment of rhabdomyosarcoma.[54,61,70]
Some general treatment considerations from the Pleuropulmonary Blastoma Registry include the following:[53,54]
  1. Type I and Type Ir: Surgery is the treatment of choice for Type I and Type Ir pleuropulmonary blastoma. In the Pleuropulmonary Blastoma Registry series, the 5-year disease-free survival (DFS) and OS were 82% and 91%, respectively. Approximately 10% of the cases may progress to Type II or Type III after surgery, but adjuvant chemotherapy does not appear to have an impact on the rate of progression and survival.[54,61]
  2. Type II and Type III: A multimodal sarcoma approach is recommended for Types II and III pleuropulmonary blastoma, usually including rhabdomyosarcoma regimens and either upfront or delayed surgery.[54,61,62] Anthracycline-containing regimens appear to be superior.[61] The respective 5-year DFS and OS were 59% and 71% for Type II and 37% and 53% for Type III.[54] The role of radiation therapy is not well defined. While the use of radiation did not impact survival in the pleuropulmonary blastoma registry series, only 20% of patients with Types II and III received it.[54] Approximately 50% of relapses occur in the brain.[54]
Treatment Options Under Clinical Evaluation
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
  • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 3,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.
    Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).

Esophageal Tumors

Incidence and Histology

Esophageal cancer is rare in the pediatric age group, although it is relatively common in older adults.[71,72] Most of these tumors are squamous cell carcinomas, although sarcomas can also arise in the esophagus. The most common benign tumor is leiomyoma.

Risk Factors, Clinical Presentation, and Diagnostic Evaluation

Risk factors include caustic ingestion, gastroesophageal reflux, and Barrett esophagus.[72] Symptoms are related to difficulty in swallowing and associated weight loss. Diagnosis is made by histologic examination of biopsy tissue.

Treatment

Treatment options for esophageal carcinoma include the following:[72]
  1. External-beam intracavitary radiation therapy.
  2. Chemotherapy (agents commonly used to treat carcinomas such as platinum derivatives, paclitaxel, and etoposide).
  3. Surgery.
Prognosis is generally poor for this cancer, which rarely can be completely resected.

Treatment Options Under Clinical Evaluation

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
  • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 3,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.
    Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).
(Refer to the PDQ summary on adult Esophageal Cancer Treatment for more information.)

Thymoma and Thymic Carcinoma

Thymoma and thymic carcinoma originate within the epithelial cells of the thymus, resulting in an anterior mediastinal mass. The term thymoma is customarily used to describe neoplasms that show no overt atypia of the epithelial component, whereas, a thymic epithelial tumor that exhibits clear-cut cytologic atypia and histologic features no longer specific to the thymus is known as thymic carcinoma or type C thymoma. Thymic carcinomas have a higher incidence of capsular invasion and metastases.[73-75] Other tumors that involve the thymus gland include lymphomas, germ cell tumors, carcinomas, and carcinoids. Hodgkin lymphoma and non-Hodgkin lymphoma may also involve the thymus and must be differentiated from true thymomas and thymic carcinomas.

Thymoma

Incidence and Outcome
Primary tumors of the thymus are exceptionally rare in children; very few pediatric series have been reported.[73,76-78]
The following studies have reported on outcomes associated with thymoma:
  • A review of the SEER registry from 1973 to 2008 identified 73 cases of malignant anterior mediastinal tumors in patients younger than 20 years.[76] Of these cases, 32% were thymoma, 29% were non-Hodgkin lymphoma, and 22% were Hodgkin lymphoma. Patients with thymoma had a worse survival at 10 years than did patients with lymphoma. Patients with thymoma who were treated in an earlier era from 1973 to 1989 had a 10-year survival rate of 18%; patients who were treated between 1991 and 2008 had a 75% survival rate. Presence of metastatic disease and treatment without surgery were associated with a worse outcome.
  • A review of 48 published cases of thymoma in patients younger than 18 years, excluding thymic carcinoma, found an association between stage of disease and survival; it also suggested guidelines for treatment. The overall 2-year survival in this series was 71%.[77]
  • The European Cooperative Study Group for Pediatric Rare Tumors identified 16 children with thymoma between 2000 and 2012.[78] Complete resection was achieved in 11 of 16 patients with thymoma. Fourteen of the 16 patients with thymoma were alive and well at a median of 5 years from diagnosis.
Clinical Presentation
These neoplasms are usually located in the anterior mediastinum and discovered during a routine chest x-ray. Symptoms may include the following:[77]
  • Cough.
  • Difficulty with swallowing.
  • Tightness of the chest.
  • Chest pain.
  • Shortness of breath
  • Superior vena cava syndrome.
About 40% of adults with thymoma have one or more paraneoplastic disorders during their lifetime.[79,80] The most common associated disorder is myasthenia gravis, which occurs in approximately 30% of adult patients.[79] This disorder has also been reported in children and is important to recognize it before a thoracotomy of a suspected thymoma. Various other paraneoplastic syndromes have been found to be associated with thymoma. These include pure red cell aplasia, hypogammaglobulinemia, nephrotic syndrome, and autoimmune or immune disorders such as scleroderma, dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, and thyroiditis. Endocrine disorders associated with thymoma include hyperthyroidism, Addison disease, and panhypopituitarism.[79-81]
Treatment
Treatment options for thymoma include the following:
  1. Surgery. Surgery is the mainstay of therapy and an attempt should be made to resect all disease.[82]
  2. Radiation therapy. Thymoma is relatively radiosensitive, and radiation therapy is recommended for patients with unresectable or incompletely resected invasive disease.[81] Radiation dosage recommendations are based on the age of the child and the extent of tumor invasion. Total doses of 45 Gy to 50 Gy are recommended for control of clear or close margins, 54 Gy for microscopically positive margins, and doses of at least 60 Gy for patients with bulky residual disease.[83]
  3. Chemotherapy. Chemotherapy is usually reserved for patients with advanced-stage disease who have not responded to radiation therapy or corticosteroids. Agents that have been effective include doxorubicin, cyclophosphamide, etoposide, cisplatin, ifosfamide, and vincristine.[73,81,84] Responses to regimens containing combinations of some of these agents have ranged from 26% to 100%, and survival rates have been as high as 50%.[83-86]
  4. Octreotide. Because thymoma shows high uptake of indium In 111–labeled octreotide, trials using this somatostatin analogue have been conducted in patients with refractory disease. In an Eastern Cooperative Oncology Group phase II trial of 42 patients, 4 patients had partial responses to octreotide alone and 8 patients responded with the addition of prednisone to octreotide.[87]
  5. Sunitinib. In an open-label phase II study of sunitinib in adult patients with refractory thymoma, partial responses were observed in 6% of patients with thymoma, and stable disease was achieved in 75% of patients with thymoma.[88]
Treatment Options Under Clinical Evaluation
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
  • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 3,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.
    Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).

Thymic Carcinoma

The European Cooperative Study Group for Pediatric Rare Tumors identified 20 patients with thymic carcinoma between 2000 and 2012.[78] Complete resection was achieved in 1 of 20 patients with thymic carcinoma. Five patients with thymic carcinoma survived. Five-year OS for patients with thymic carcinoma was 21.0%.
Treatment
Treatment options for thymic carcinoma include the following:
  1. Surgery. Surgery is the mainstay of therapy and an attempt should be made to resect all disease.[82]
  2. Radiation therapy. Thymic carcinoma is relatively radiosensitive, and radiation therapy is recommended for patients with unresectable or incompletely resected invasive disease.[81] Radiation dosage recommendations are based on the age of the child and the extent of tumor invasion. Total doses of 45 Gy to 50 Gy are recommended for control of clear or close margins, 54 Gy for microscopically positive margins, and doses of at least 60 Gy for patients with bulky residual disease.[83]
  3. Chemotherapy (as described for thymoma). Response rates are lower for patients with thymic carcinoma, but 2-year survival rates have been reported to be as high as 50%.[86,89,90]
  4. Sunitinib. In an open-label phase II study of sunitinib in adult patients with refractory thymic carcinoma, partial responses were observed in 26% of patients with thymic carcinoma and stable disease was achieved in 65% of patients with thymic carcinoma.[88]
(Refer to the PDQ summary on adult Thymoma and Thymic Carcinoma Treatment for more information on the treatment of thymoma and thymic carcinoma.)
Treatment Options Under Clinical Evaluation
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
  • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 3,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.
    Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).

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